Manufacture of phosphoric esters of polyhydric alcohols



Patented A g. 3 1, 1925.

, UNITED STATES,

.PAT'ENT OFFICE.

PAUL EMILE GOISSEDE'I. AND ANDRE LOUIS HUBSON, OF LYO NS, FBANCE, ASBIGNOBB TO SOCIETE CHIHIQUE DES USINES DU RHONE, F PARIS, FRANCE.

MANUFACTURE OF PHOSPKORIC ESTERS OF POLYHYDRIC ALCOHOLS.

No Drawing. Application filed September 15, 1925, Serial No. 58,443, and in France April 27, 1925.

No. 247,809 of the 31rd February 1910) re pare the glucose and saccharose monop osphoric esters by the action, at low tempera-.-

Io ture, of phosphorous oxychloride on sugar in aqueous solution, in presence of calcium carbonate or of lime. In this manner the calcium salt of the hosphoric combination is formed and this, being insoluble in alco- IB hol, is separated from the concentrated reacting solution by precipitation with alcohol. lln this manner of proceeding, this calcium salt is obtained in presence of large quantities of calcium chloride which con- 2 taminate the precipitate from which it can be entirely eliminated only by repeated precipitation and washings with alcohol.

With levulose, lactose and maltose the elimination of the calcium chloride becomes practically impossible owing to the formation of stable combinations of the hosphoric product with the calcium chlori e, as has been recognized by Neuberg and Ketschimer '(Bioch. 'Zeitschriftg 1911 vol. 36,

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he present invention has for its object a new process of fabrication of the phosphoric esters of carbohydrates and polyvalent alcohols, which gives good yields and which permits the isolation of these products directly in the state of calcium salts without having recourse to a delicate and costly purification. It consists in treating the carbohydrates and the polyvalent alcohols with phosphoric an hydride in presence of anhydrous tertiary bases, such as pyridine and its homolo ues.

Applicants have found that when per mming the combination in these conditions, one obtains the sought product with great regularity; this result is ve remarkable, for if the hosphoric anhydri e is caused to react on t ese bodies, either directly or in the presence of usual solvents such as benzene or toluene, only poor results were obtained owin to the too. energetic condensing and deh dratin action of this anhydride.

arbohy rate or polyvalent alcohol may be dissolved in the reacting medium or suspended therein.- One may utilize either a ll pure tertiary base, or a mixture ofi several such bases, which maybe diluted with a solvent which does not react chemically on the other bodies present.

A few examples, illustrating the manner in which the process is carried out, are 00 given hereunder, it being well understood that these examples are in no way limitative.

' Example l.-Glucose: kilos of dry glucose are dissolved in kilos of pyridine and are introduced in an apparatus rovided with a stirrer, 7.800-kilos of p osphoric anhydride in suspension in 2 kilos of pyridine are added. The mixture is heated for a' few hours at (SO-65 C. and the excess of yridine is subsequently distilled. After coo ing, 50 litres of water are added, and the a ueous solution is saturated with-carbonate o lime. It is filtered and concentrated in vacuo at a low temperature. The glucose monophosphate of calcium is then precipitated directly with alcohol.

Ewample I1 .llevulose: by replacing in the preceding example glucose by levulose, levulose monophosphate of calcium is obtained in similar conditions.

Ewa/mple IlI.-Saccharose: 10 kilos pulverized saccharose, dried in an oven for several hours at C. are suspended in 30 kilos of anhydrous pyridine, 4,500 hosphoric anhydride in suspension in 1 hilos of pyri- W dine are added. The mixture is heated to 100 C. during several hours with stirring and the excess of pyridine is afterwards distilled.

The residue is treated with water and no saturated with milk of lime, filtered and concentrated in vacuo. lhe saccharose monophosphate of calcium is then precipitated with alcohol.

Ema m Ze lV.--By replacing in Example HI sacc arose by lactose, lactose monophoshate of calcium is obtained in similar conitions.

Ewample V.-Mannite. (a) monophosphoric ester; 2 kilos of mannite dried in an oven are suspended in 8 kilos of pyridine. The mixture is introduced in a stirred vessel and 1.600 kilos of phosphoric anhydride is added. The temperature is raised to about 110.-115 C. with stirring. At the end ofthe operation the pyridine and the residue is dissolved in water. The solution is neutralized with milk of lime which frees the pyridine from its phosphoric combinations and forms the mannite-monophosphate of calcium isolated in the form of a white powder very soluble in water.

Diphosphoric-ester: By using in the preceding example a double quantity of phosphoric anhydride, a phosphoric ester is isolated which corresponds to mannite diphosphoric ester.

The preceding examples show that the process is general and permits the calcium salt of the phosphoric esters of the carbohydra-tes and of the polyvalent alcohols to be very easily isolated and with good yields.

Particularly, it allows the n'ianufaciure, by direct esterification, of the monophoshoric esters of levulose and lactose, which it iiad not been possible to obtain directly hitherto.

What we claim and desire to secure by Letters Patent is 1. A process of manufacture of phosphoric esters of polyvalent alcohols consisting in treating these polyvalent alcohols by phosphoric anhydride in presence of tertiary bases and separating the esters obtained from the reacting medium by precipitating their calcium salt.

2. A process of manufacture of phosphoric esters of polyvalent alcohols consisting in treating these polyvalent alcohols by phosphoric anhydride in presence of a compound of the pyridine series, and separating the ester so obtained from the reacting medium by precipitating their calcium salt.

3. A process of manufacture of phosphoric esters of polyvalcnt alcohols consisting in treating these polyvalent alcohols by phosphoric anhydride in presence of pyridine, and separating the esters obtained from the reacting medium by precipitating their calcium salt.

4:. A process for the manufacture of a phosphoric ester of glucose, consisting in treating glucose with phosphoric anhydride in presence of a tertiary base, and separating the ester by means of carbonate of calmom.

5. A process for the manufacture of a phosphoric ester of glucose, consisting in treating glucose with phosphoric anhydride in presence of a compound of the pyridine series, and separating the ester by means of carbonate of calcium.

. 6. A process for the manufacture of a phopsphoric ester of glucose, consisting in treating glucose with phosphoric anhydride in presence of pyridine and separating the ester by means of carbonate of calcium.

7. A process for the manufacture of glucose monophosphate of calcium consisting in treating glucose with phosphoric anhydride in presence of pyridine and separating the ester by means of carbonate of calcium.

In testimony whereof we have signed our names to this specification.

PAUL EMILE GOISSEDET. ANDRE LOUIS HUSSON. 

